P1332: PROMISING OUTCOME OF PATIENTS OLDER THAN 70 YEARS WHO UNDERWENT PERIPHERAL BLOOD HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR ACUTE MYELOID LEUKEMIA OR HIGH RISK MYELODYSPLASTIC SYNDROME
Authors: S. Harbi, L. Brac de la perriere, S. Garciaz, T. Pagliardini, B. Calmels, M. Cecile, Y. Hicheri, B. Bouchacourt, A. Calleja, F. Dachy, S. Fürst, C. Lemarie, C. Braticevic, G. Morel, F. Legrand, E. Bekrieva, A. Granata, P. J. Weiller, C. Chabannon, N. Vey, D. Blaise, R. Devillier
Journal: HemaSphere (2022)

Background: Allogeneic stem cell transplantation is a curative option of patients older than 60 years of age with AML and high risk MDS. In this situation, the development of haploidentical transplantation (Haplo-SCT) using post transplantation cyclophosphamide (PT-Cy) allowed extending the feasibility of Allo-HSCT. However, there is few data specifically focusing on Haplo-SCT in patients over 70 years of age with AML and MDS, for whom the benefit-risk balance of Haplo-SCT is still a matter of debate. Aims: To evaluate the outcome of patients older than 70 years with AML or high risk MDS who underwent Haplo-SCT. Methods: This retrospective study included consecutive AML or MDS patients older than 70 years who received first Haplo-SCT from 2013 to 2021 in our center. All patients had the same transplantation modalities: 1) Non-myeloablative conditioning regimen as described by the Baltimore's group (Fludarabine, cyclophosphamide and 2-Gray TBI); 2) Peripheral blood stem cells (PBSC) as graft source; 3) GVHD prophylaxis using PT-Cy, cyclosporine A and mycophenolate mofetil; 4) G-CSF from day+5 to neutrophil recovery. Prophylactic donor lymphocyte infusion (DLI) was initially planned after day+60 in absence of GVHD. Results: We analyzed 45 patients who met inclusion criteria, 23 with AML and 22 with MDS. The median age was 72 years (range: 70-75). HCT-CI was >= 3 in 22 patients (49%). At the time of Haplo-SCT, 22/23 AML patients were in CR (17 CR1 and 5 CR2) and one patient had refractory AML. Disease status at Haplo-SCT was CR, PR, marrow CR and active disease in 12, 2, 1 and 7 patients, respectively. All patients received pre transplantation treatment with intensive chemotherapy and/or azacytidine, except one MDS patients who underwent upfront Haplo-SCT. Disease risk index was high or very high in 11 patients (24%), and intermediate in 34 patients (76%). Median follow up using the reverse Kaplan Meier method was 36 months (95%CI: 25-43). Grade 2-4 and 3-4 acute GVHD at day+100 was 33% and 7%, respectively. There was no early death (at day+100: OS=100%; NRM=0%). At 3 years after Haplo-SCT, the cumulative incidence of all grades and moderate to severe chronic GVHD was 37% and 28%. Half of the cases of chronic GVHD occurred after prophylactic DLI. The 3-year cumulative incidence of NRM was 20%. In AML patients, the 3-year CIR, PFS and OS were 17%, 61% and 64% respectively. Corresponding values for MDS patients were 26%, 56% and 66%, respectively. Ten patients received prophylactic DLI. Among them, one died from late NMR (urothelial metastatic cancer after 2 years post Haplo-SCT) and one patient relapsed and subsequently died from AML (complex karyotype, CR2). The 8 remaining patients who received prophylactic DLI are still disease free at last follow up. As surrogate marker of quality of life, we evaluated the prevalence of GVHD and immunosuppressive treatment (IST) in disease free patients. At 2 years after Haplo-SCT, 87% of disease free patients are living without GVHD and without IST. Summary/Conclusion: Haplo-SCT in patients older than 70 years with AML or high risk MDS is feasible without early NRM. The use of PBSC and prophylactic DLI may explain the low incidence of relapse and long-term survival. Our results support that selected patients older than 70 years can achieve promising outcomes after non-myeloablative Haplo-SCT using PBSC, confirming that age by itself and the absence of an HLA-matched donor should not be considered as firm contraindication for transplantation.